Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). Biofilm infections constitute a number of clinical challenges, including diseases involving uncultivable species, chronic inflammation, impaired wound healing, rapidly generated multiple drug resistant (MDR) strains, and the spread of infectious emboli. This immune engineering approach to preventing medical device-based infections will be developed for two model MDR bacterial systems: Staphylococcus aureus (SA) (as seen on cardio-vascular devices and MRSA infections) and Pseudomonas aeruginosa (PA) (representative carbapenem-resistant Enterobacteriaceae - CRE; as seen on ventillators, endotracheal devices, catheters). Model biomaterial implants will release synthetic opsonins; bi-specific fusion complexes (BiFCs) designed to bind together invading bacteria with neutrophils and/or macrophages (M) while stimulating phagocytosis.